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Am J Nucl Med Mol Imaging 2013;3(4):372-383
Original Article
Design, synthesis and in vitro characterization of fluorescent and paramagnetic
CXCR4-targeted imaging agents
Ole Tietz, Nazila Kamaly, Graham Smith, Elham Shamsaei, Kishore K Bhakoo, Nicholas J Long, Eric O Aboagye
Department of Surgery and Cancer, Comprehensive Cancer Imaging Centre, Hammersmith Hospital, Imperial College London,
London, W12 0NN, UK; Translational Molecular Imaging Group, Singapore Bioimaging Consortium, Agency for Science, Technology
and Research, Singapore 138667; Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
These authors contributed equally to this work.
Received February 27, 2013; Accepted June 21, 2013; Epub July 10, 2013; Published July 15, 2013
Abstract: The G-protein coupled C-X-C chemokine receptor type 4 (CXCR4) is highly overexpressed in a range of cancers and is
therefore an excellent biomarker for cancer imaging. To this end targeted iron oxide nanoparticles were developed and utilised for in
vitro imaging of MDA-MB-231 breast cancer cells overexpressing the CXCR4 receptor. Nanoparticles comprising an iron oxide core,
encapsulated in a stabilising epichlorohydrin crossed-linked dextran polymer, were conjugated to a cyclopentapeptide with affinity to
the CXCR4 receptor. The particles were characterized for their size, surface charge and r2 relaxivity at 4.7 T. MR imaging of the
CXCR4 receptor with targeted iron oxide nanoparticles revealed an approximately 3-fold increase in T2 signal enhancement of
MDA-MB-231 cells compared to non-targeted controls. Prussian blue staining of labeled MDA-MB-231 cells revealed darker and
more intense staining of the cellular membrane. This study demonstrates the potential of targeted iron oxide nanoparticles for the
imaging of the CXCR4 receptor by magnetic resonance imaging (MRI). (ajnmmi1302006).
Keywords: CXCR4, iron oxide nanoparticles, tumor MRI, targeted nanoparticles, T2 imaging, cyclopentapeptide
Address correspondence to: Dr. Nicholas J Long, Department of Chemistry, Imperial College London, South Kensington, London,
SW7 2AZ, UK. Phone: +44 (0) 20 7594 5781; Fax: +44 (0) 20 7594 5804; E-mail: n.long@imperial.ac.uk; Dr. Eric O Aboagye,
Department of Surgery and Cancer, Comprehensive Cancer Imaging Centre, Imperial College London, Hammersmith Hospital, Du
Cane Road, East Acton, London, W12 0NN, UK. Phone: +44 (0) 20 8383 3759; Fax: +44 (0) 20 8383 1783; E-mail:
eric.aboagye@imperial.ac.uk
Original Article
Design, synthesis and in vitro characterization of fluorescent and paramagnetic
CXCR4-targeted imaging agents
Ole Tietz, Nazila Kamaly, Graham Smith, Elham Shamsaei, Kishore K Bhakoo, Nicholas J Long, Eric O Aboagye
Department of Surgery and Cancer, Comprehensive Cancer Imaging Centre, Hammersmith Hospital, Imperial College London,
London, W12 0NN, UK; Translational Molecular Imaging Group, Singapore Bioimaging Consortium, Agency for Science, Technology
and Research, Singapore 138667; Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
These authors contributed equally to this work.
Received February 27, 2013; Accepted June 21, 2013; Epub July 10, 2013; Published July 15, 2013
Abstract: The G-protein coupled C-X-C chemokine receptor type 4 (CXCR4) is highly overexpressed in a range of cancers and is
therefore an excellent biomarker for cancer imaging. To this end targeted iron oxide nanoparticles were developed and utilised for in
vitro imaging of MDA-MB-231 breast cancer cells overexpressing the CXCR4 receptor. Nanoparticles comprising an iron oxide core,
encapsulated in a stabilising epichlorohydrin crossed-linked dextran polymer, were conjugated to a cyclopentapeptide with affinity to
the CXCR4 receptor. The particles were characterized for their size, surface charge and r2 relaxivity at 4.7 T. MR imaging of the
CXCR4 receptor with targeted iron oxide nanoparticles revealed an approximately 3-fold increase in T2 signal enhancement of
MDA-MB-231 cells compared to non-targeted controls. Prussian blue staining of labeled MDA-MB-231 cells revealed darker and
more intense staining of the cellular membrane. This study demonstrates the potential of targeted iron oxide nanoparticles for the
imaging of the CXCR4 receptor by magnetic resonance imaging (MRI). (ajnmmi1302006).
Keywords: CXCR4, iron oxide nanoparticles, tumor MRI, targeted nanoparticles, T2 imaging, cyclopentapeptide
Address correspondence to: Dr. Nicholas J Long, Department of Chemistry, Imperial College London, South Kensington, London,
SW7 2AZ, UK. Phone: +44 (0) 20 7594 5781; Fax: +44 (0) 20 7594 5804; E-mail: n.long@imperial.ac.uk; Dr. Eric O Aboagye,
Department of Surgery and Cancer, Comprehensive Cancer Imaging Centre, Imperial College London, Hammersmith Hospital, Du
Cane Road, East Acton, London, W12 0NN, UK. Phone: +44 (0) 20 8383 3759; Fax: +44 (0) 20 8383 1783; E-mail:
eric.aboagye@imperial.ac.uk
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